Synthesis of 6-aryltetrahydropyran-2,4-diones containing a hexamethylene substituent in positions 3 or 5 of heterocycle

Article abstract of DOI:10.1134/S1070428008070191

Methyl 3-(1-bromocycloheptyl)-2,2-dimethyl-3-oxopropanoate and methyl 1-(2-bromo-2-methylpropanoyl)cycloheptanecarboxylates react with zinc and arylcarbaldehydes yielding 5-aryl-2,2-dimethyl-4-oxaspiro[5.6]dodecan-1.3-diones and 3-aryl-4,4-dimethyl-2-oxaspiro[5.6]dodecan-1.5-diones respectively.

Full text of DOI:10.1134/S1070428008070191

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 7, pp. 1061−1063. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.F. Kirillov, V.S. Melekhin, D.V. Bogatyrev, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 7, pp. 1071−
1073.
Synthesis of 6-Aryltetrahydropyran-2,4-diones Containing
a Hexamethylene Substituent in Positions 3 or 5 of Heterocycle
N. F. Kirillov, V. S. Melekhin, and D. V. Bogatyrev
Perm State University, Perm, 614990 Russia
Received December 25, 2007
Abstract— Methyl 3-(1-bromocycloheptyl)-2,2-dimethyl-3-oxopropanoate and methyl 1-(2-bromo-2-
methylpropanoyl)cycloheptanecarboxylates react with zinc and arylcarbaldehydes yielding 5-aryl-2,2-dimethyl-
4-oxaspiro[5.6]dodecan-1.3-diones and 3-aryl-4,4-dimethyl-2-oxaspiro[5.6]dodecan-1.5-diones respectively.
DOI: 10.1134/S1070428008070191
In extension of previous research on preparation of
substituted tetrahydropyran-2,4-diones possessing in
positions 3 or 5 of the heterocycle a spiro carbon atom
included into a five- or six-memebered ring [1–3] we
synthesized analogous compounds containing in these
positions a hexamethylene substituent.
dimethyl-3-oxopropanoate (II). Bromo derivative II in
reaction with zinc formed a zinc enolate III that added
to the carbonyl group of aromatic aldehydes providing
intermediates IVa–IVd. The latter under the reaction
conditions spontaneously transformed into the target
tetrahydropyran-2,4-diones with a hexamethylene
substituent in the position 5 of the heterocycle, namely,
into 5-aryl-2,2-dimethyl-4-oxaspiro[5.6]dodecene-1,3-
diones Va–Vd.
Under the conditions of Reformatsky reaction
proceeding from methyl 2-bromo-2-methylpropanoate,
zinc, and cycloheptanecarbonyl chloride a methyl 2,2-
dimethyl-3-oxo-3-cycloheptylpropanoate (I) was
obtained that by bromination was converted into the key
bromo derivative, methyl 3-(1-bromocycloheptyl)-2,2-
Similarly from the methyl 1-bromocycloheptane-
carboxylate, zinc, and a 2-methylpropanoyl chloride
a methyl 1-(2-methylpropanoyl)cycloheptanecarboxylate
Zn,
COCl
Me
Br
Br2
COCMe2COOMe
C
COOMe
_
_
Me
ZnBrCl
HBr
COCMe2COOMe
Br
I
II
O
O
OZnBr
Me
Zn
ArCHO
Me
C
CMe2COOMe
_
MeOZnBr
Ar
Me
H
Me
O
O
OZnBr
III
O
Ar
MeO
_
_
Va Vd
IVa IVd
Ar = Ph (a), 4-BrC6H4 (b), 4-ClC6H4 (c), 4-MeOC6H4 (d).
1061

KIRILLOV et al.
COCHMe2
1062
Br
Zn, Me2CHCOCl
COCBrMe2
COOMe
Br2
_
_
ZnBrCl
HBr
COOMe
COOMe
VI
VII
OZnBr
O
O
Me
Me
Me
Me
Zn
Me
Ar
ArCHO
Me
_
MeOZnBr
COOMe
O
H
O
O
OMe
OZnBr
Ar
VIII
_
_
Xà Xc
IXà IXc
Ar = 4-BrC6H4 (a), 4-ClC6H4 (b), 3-NO2C6H4 (c).
(VI) was obtained that was converted into bromo deriva-
tive VII. Further by the reaction of bromo derivative VII,
zinc, and aromatic aldehydes via intermediate compounds
VIII and IX we synthesized tetrahydropyran-2,4-diones
with the hexamethylene substituent in the position 3 of
the heterocycle, 3-aryl-4,4-dimethyl-2-oxaspiro[5.6]-
dodecene-1,5-diones Xa–Xc.
solvent was distilled off, and the reaction product was
twice distilled in a vacuum. Yield 15.4 g (68%), bp 128–
130°C (10 mm Hg), d240 1.0164, nD20 1.4660. IR spectrum,
1
ν, cm–1: 1705, 1725 (C=O). H NMR spectrum, δ, ppm:
3.71 s (3H, OMe), 2.64–2.76 m (1H, CHCO), 1.36 s (6H,
2Me), 1.33–1.82 m [12H, (CH2)6]. Found, %: C 69.26;
H 9.69. C13H22O3. Calculated, %: C 68.99; H 9.80.
Methyl 1-(2-methylpropanoyl)cycloheptane-
carboxylate (VI) was obtained analogously to compound
I. As initial compounds were used methyl 1-bromo-
cycloheptanecarboxylate and 2-methylpropanoyl
chloride. Yield 10.6 g (47%), bp 131– 133°C (10 mm
Hg), d420 1.0262, nD20 1.4712. IR spectrum, ν, cm–1: 1710,
The yields of reaction products attained 48–67%. The
composition and structure of compounds obtained were
proved by elemental analysis, IR and 1H NMR spectra.
In the IR spectra of aryltetrahydropyran-2,4-diones
characteristic absorption bands of ketone carbonyls were
present at 1705–1710 cm–-1, and of lactone carbonyl
1
1
groups, in the region 1730–1745 cm–1. In H NMR
1725 (C=O). H NMR spectrum, δ, ppm: 3.66 s (3H,
OMe), 2.59–2.92 m (1H, CHCO), 1.42– 2.15 m [12H,
(CH2)6], 1.03 d (6H, 2Me, J 7.4 Hz). Found, %: C 69.15;
H 9.89. C13H22O3. Calculated, %: C 68.99; H 9.80.
spectra a characteristic singlet of the methine proton
appeared in the region 5.19–5.46 ppm.
EXPERIMENTAL
Methyl 3-(1-bromocycloheptyl)-2,2-dimethyl-3-
oxopropanoate (II). To a solution of 0.05 mol of
compound I in 20 ml of acetic acid was added 0.055 mol
of bromine, the mixture was heated on a water bath for
1 h, acetic acid and excess bromine were distilled off,
and the reaction product was distilled in a vacuum. Yield
11.0 g (72%), mp 56–57°C. IR spectrum, ν, cm–1: 1710,
IR spectra of compounds I, II, Va–Vd, VI, VII, Xa–
Xc were recorded on a spectrophotometer Specord 75IR
1
from mulls in mineral oil. H NMR spectra of these
compounds were registered from solutions in CDCl3 on
a spectrometer Tesla BS-576A (100 MHz), internal
reference HMDS.
1
1750 (C=O). H NMR spectrum, δ, ppm: 3.66 s (3H,
OMe), 1.50 s (6H, 2Me), 1.30–2.40 m [12H, (CH2)6].
Found, %: C 50.88; H 7.07; Br 25.97. C13H21BrO3.
Calculated, %: C 51.16; H 6.94; Br 26.18.
Methyl 2,2-dimethyl-3-oxo-3-cycloheptyl-
propanoate (I). To 10 g of fine zinc turnings in 25 ml of
anhydrous benzene and 10 ml of anhydrous ethyl acetate
was added 0.1 mol of methyl 2-bromo-2-methyl-propano-
ate and 0.1 mol cycloheptanecarbonyl chloride in 50 ml
of benzene. The mixture was boiled for 1 h, it was then
decanted and hydrolyzed with water. The organic layer
was separated, dried with anhydrous sodium sulfate, the
Methyl 1-(2-bromo-2-methylpropanoyl)cyclo-
heptanecarboxylate (VII) was similarly obtained using
as initial compound ester VI. Yield 10.7 g (70%), mp 49–
51°C. IR spectrum, ν, cm–1: 1715, 1735 (C=O). 1H NMR
spectrum, δ, ppm: 3.65 s (3H, OMe), 1.88 s (6H, 2Me),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 7 2008

SYNTHESIS OF 6-ARYLTETRAHYDROPYRAN-2,4-DIONES
1063
H 8.04. C20H26O4. Calculated, %: C 72.70; H 7.93.
1.41–2.32 m [12H, (CH2)6]. Found, %: C 50.95; H 7.11;
Br 26.31. C13H21BrO3. Calculated, %: C 51.16; H 6.94;
Br 26.18.
3-Aryl-4,4-dimethyl-2-oxaspiro[5.6]dodecene-1,5-
diones Xa–Xc were prepared similarly to compounds V.
Bromooxoester VII was used as initial compound. In
the preparation of compound Xc the 3-nitrobenzaldehyde
was added after heating compound VII with zinc for
30 min.
5-Aryl-2,2-dimethyl-4-oxaspiro[5.6]dodecene-1,3-
diones Va–Vd. To a mixture of 1 g of fine zinc turnings,
catalytic quantity of mercuric chloride, and 30 ml of
anhydrous ethyl acetate was added dropwise at stirring
a mixture of 10 mmol of compound II and 9.6 mmol of
an appropriate aldehyde in 15 ml of anhydrous ethyl
acetate. The reaction mixture was boiled for 2 h, cooled,
decanted from excess zinc, and hydrolyzed with 5%
hydrochloric acid. The organic layer was separated, the
reaction products were twice extracted from the water
layer into ethyl acetate. The combined organic solution
was dried with anhydrous sodium sulfate, ethyl acetate
was distilled off, and compounds Va–Vd were recrystal-
lized from methanol.
3-(4-Bromophenyl)-4,4-dimethyl-2-oxaspiro[5.6]-
dodecene-1,5-dione (Xa). Yield 2.26 g (62%), mp 184–
185°C. IR spectrum, ν, cm–1: 1705, 1745 (C=O). 1H NMR
spectrum, δ, ppm: 7.44 d, 7.14 d (4H, 4-BrC6H4,
J 7.4 Hz), 5.31 s (1H, CHO), 1.38–2.40 m [12H, (CH2)6],
0.98 s (3H, Me), 0.93 s (3H, Me). Found, %: C 60.31;
H 6.28; Br 21.21. C19H23BrO3. Calculated, %: C 60.17;
H 6.11; Br 21.07.
4,4-Dimethyl-3-(4-chlorophenyl)-2-oxaspiro[5.6]-
dodecene-1,5-dione (Xb). Yield 1.86 g (58%), mp 200–
202°C. IR spectrum, ν, cm–1: 1710, 1745 (C=O). 1H NMR
spectrum, δ, ppm: 7.30 d, 7.18 d (4H, 4-ClC6H4,
J 8.3 Hz), 5.32 s (1H, CHO), 1.40–2.38 m [12H, (CH2)6],
0.98 s (3H, Me), 0.92 s (3H, Mε). Found, %: C 68.28;
H 7.09; Cl 10.35. C19H23ClO3. Calculated, %: C 68.15;
H 6.92; Cl 10.59.
2,2-Dimethyl-5-phenyl-4-oxaspiro[5.6]dodecene-
1,3-dione (Va). Yield 1.38 g (48%), mp 162– 163°C. IR
spectrum, ν, cm–1: 1710, 1730 (C=O). 1H NMR spectrum,
δ, ppm: 7.17–7.31 m (5H, Ph), 5.24 s (1H, CHO), 1.48 s
(6H, 2Me), 0.88–2.42 m [12H, (CH2)6]. Found, %: C 75.78;
H 7.96. C19H24O3. Calculated, %: C 75.97; H 8.05.
5-(4-Bromophenyl)-2,2-dimethyl-4-oxaspiro[5.6]-
dodecene-1,3-dione (Vb). Yield 2.18 g (60%), mp 182–
183°C. IR spectrum, ν, cm–1: 1705, 1730 (C=O). 1H NMR
spectrum, δ, ppm: 7.44 d, 7.21 d (4H, 4-BrC6H4,
J 8.4 Hz), 5.19 s (1H, CHO), 1.48 s (6H, 2Me), 0.80–
2.45 m [12H, (CH2)6]. Found, %: C 59.95; H 6.24;
Br 20.84. C19H23BrO3. Calculated, %: C 60.17; H 6.11;
Br 21.07.
4,4-Dimethyl-3-(3-nitrophenyl)-2-oxaspiro-
[5.6]dodecene-1,5-dione (Xc). Yield 1.72 g (52%), mp
157–158°C. IR spectrum, ν, cm–1: 1710, 1740 (C=O).
1H NMR spectrum, δ, ppm: 8.17 d, 8.12 s, 7.65 d, 7.49 t
(4H, 3-NO2C6H4, J 8.5 Hz), 5.46 s (1H, CHO), 1.40–
2.44 m [12H, (CH2)6], 1.04 s (3H, Me), 0.95 s (3H, Me).
Found, %: C 65.88; H 6.93; N 3.94. C19H23NO5.
Calculated, %: C 66.07; H 6.71; N 4.06.
2,2-Dimethyl-5-(4-chlorophenyl)-4-oxaspiro[5.6]-
dodecene-1,3-dione (Vc). Yield 2.15 g (67%), mp 177–
178°C. IR spectrum, ν, cm–1: 1710, 1740 (C=O).
1H NMR spectrum, δ, ppm: 7.17–7.28 m (4H, 4-ClC6H4),
5.21 s (1H, CHO), 1.48 s (6H, Me), 0.87–2.44 m [12H,
(CH2)6]. Found, %: C 68.28; H 7.09; Cl 10.35.
C19H23ClO3. Calculated, %: C 68.15; H 6.92; Cl 10.59.
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grant no.
07-03-96035).
REFERENCES
2,2-Dimethyl-5-(4-methoxyphenyl)-4-oxaspiro-
[5.6]dodecene-1,3-dione (Vd). Yield 1.62 g (51%), mp
155–156°C. IR spectrum, ν, cm–1: 1710, 1730 (C=O).
1H NMR spectrum, δ, ppm: 7.23 d, 6.82 d (4H, 4-MeOC6H4,
J 8.4 Hz), 5.19 c (1H, CHO), 3.79 c (3H, MeO), 1.47 s
(6H, 2Me), 0.90–2.44 m [12H, (CH2)6]. Found, %: C 72.52;
1. Kirillov, N.F., Shchepin, V.V., and Litvinov, D.N., Zh. Org.
Khim., 2000, vol. 36, p. 1010.
2. Kirillov, N.F. and Shchepin, V.V., Zh. Org. Khim., 2001,
vol. 37, p. 858.
3. Kirillov, N.F., Shchepin, V.V., and Vakhrin, M.I., Zh. Org.
Khim., 2004, vol. 40, p. 606.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 7 2008